MOFs-Based Materials with Confined Space: Opportunities and Challenges for Energy and Catalytic Conversion.

Metal-Organic Frameworks (MOFs) are a very promising material in the fields of energy and catalysis due to their rich active sites, tunable pore size, structural adaptability, and high specific surface area. The concepts of "carbon peak" and "carbon neutrality" have opened up huge development opportunities in the fields of energy storage, energy conversion, and catalysis, and have made significant progress and breakthroughs. In recent years, people have shown great interest in the development of MOFs materials and their applications in the above research fields. This review introduces the design strategies and latest progress of MOFs are included based on their structures such as core-shell, yolk-shell, multi-shelled, sandwich structures, unique crystal surface exposures, and MOF-derived nanomaterials in detail. This work comprehensively and systematically reviews the applications of MOF-based materials in energy and catalysis and reviews the research progress of MOF materials for atmospheric water harvesting, seawater uranium extraction, and triboelectric nanogenerators. Finally, this review looks forward to the challenges and opportunities of controlling the synthesis of MOFs through low-cost, improved conductivity, high-temperature heat resistance, and integration with machine learning. This review provides useful references for promoting the application of MOFs-based materials in the aforementioned fields.

CD3, CD8, IFN-γ, tumor and stroma inflammatory cells as prognostic indicators for surgically resected SCLC: evidences from a 10-year retrospective study and immunohistochemical analysis.

Current clinical guidelines limit surgical intervention to patients with cT1-2N0M0 small cell lung cancer (SCLC). Our objective was to reassess the role of surgery in SCLC management, and explore novel prognostic indicators for surgically resected SCLC. We reviewed all patients diagnosed with SCLC from January 2011 to April 2021 in our institution. Survival analysis was conducted using the Kaplan-Meier method, and independent prognostic factors were assessed through the Cox proportional hazard model. In addition, immunohistochemistry (IHC) staining was performed to evaluate the predictive value of selected indicators in the prognosis of surgically resected SCLC patients. In the study, 177 SCLC patients undergoing surgical resection were ultimately included. Both univariate and multivariate Cox analysis revealed that incomplete postoperative adjuvant therapy emerged as an independent risk factor for adverse prognosis (p < 0.001, HR 2.96). Survival analysis revealed significantly superior survival among pN0-1 patients compared to pN2 patients (p < 0.0001). No significant difference in postoperative survival was observed between pN1 and pN0 patients (p = 0.062). Patients with postoperative stable disease (SD) exhibited lower levels of tumor inflammatory cells (TIC) (p = 0.0047) and IFN-γ expression in both area and intensity (p < 0.0001 and 0.0091, respectively) compared to those with postoperative progressive disease (PD). Conversely, patients with postoperative SD showed elevated levels of stromal inflammatory cells (SIC) (p = 0.0453) and increased counts of CD3+ and CD8+ cells (p = 0.0262 and 0.0330, respectively). Survival analysis indicated that high levels of SIC, along with low levels of IFN-γ+ cell area within tumor tissue, may correlate positively with improved prognosis in surgically resected SCLC (p = 0.017 and 0.012, respectively). In conclusion, the present study revealed that the patients with pT1-2N1M0 staging were a potential subgroup of SCLC patients who may benefit from surgery. Complete postoperative adjuvant therapy remains an independent factor promoting a better prognosis for SCLC patients undergoing surgical resection. Moreover, CD3, CD8, IFN-γ, TIC, and SIC may serve as potential indicators for predicting the prognosis of surgically resected SCLC.

Direct Observation of All Open-Shell Intermediates in a Photocatalytic Cycle.

Molecular photocatalysis has shown tremendous success in sustainable energy and chemical synthesis. However, visualizing the transient open-shell intermediates in photocatalysis is a significant and long-standing challenge. By employing our recently developed innovative time-resolved electron paramagnetic resonance technique, we directly observed all radicals and radical ions involved in the photocatalytic addition of pempidine to tert-butyl acrylate. The full picture of the photocatalytic cycle is vividly illustrated by the fine structures, chemical kinetics, and dynamic spin polarization of all open-shell intermediates directly observed in this prototypical system. Given the universality of this methodology, we believe it greatly empowers the research paradigm of direct observation in both photocatalysis and radical chemistry.

CT radiomics-based model for predicting TMB and immunotherapy response in non-small cell lung cancer.

BACKGROUND: Tumor mutational burden (TMB) is one of the most significant predictive biomarkers of immunotherapy efficacy in non-small cell lung cancer (NSCLC). Radiomics allows high-throughput extraction and analysis of advanced and quantitative medical imaging features. This study develops and validates a radiomic model for predicting TMB level and the response to immunotherapy based on CT features in NSCLC. METHOD: Pre-operative chest CT images of 127 patients with NSCLC were retrospectively studied. The 3D-Slicer software was used to outline the region of interest and extract features from the CT images. Radiomics prediction model was constructed by LASSO and multiple logistic regression in a training dataset. The model was validated by receiver operating characteristic (ROC) curves and calibration curves using external datasets. Decision curve analysis was used to assess the value of the model for clinical application. RESULTS: A total of 1037 radiomic features were extracted from the CT images of NSCLC patients from TCGA. LASSO regression selected three radiomics features (Flatness, Autocorrelation and Minimum), which were associated with TMB level in NSCLC. A TMB prediction model consisting of 3 radiomic features was constructed by multiple logistic regression. The area under the curve (AUC) value in the TCGA training dataset was 0.816 (95% CI: 0.7109-0.9203) for predicting TMB level in NSCLC. The AUC value in external validation dataset I was 0.775 (95% CI: 0.5528-0.9972) for predicting TMB level in NSCLC, and the AUC value in external validation dataset II was 0.762 (95% CI: 0.5669-0.9569) for predicting the efficacy of immunotherapy in NSCLC. CONCLUSION: The model based on CT radiomic features helps to achieve cost effective improvement in TMB classification and precise immunotherapy treatment of NSCLC patients.

Association of antenatal corticosteroids with mortality and morbidities in very preterm infants born to women with hypertensive disorders of pregnancy: a multicenter prospective cohort study.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) is the most common cause of indicated preterm delivery, but the impact of prenatal steroid exposure on the outcomes of preterm infants born to HDP mothers, who may be at risk for intrauterine hypoxia-ischemia, remains uncertain. The study objective is to evaluate the mortality and morbidities in HDP for very preterm infants (VPIs) exposed to different course of ANS. METHODS: This is a prospective cohort study comprising infants with < 32 weeks gestation born to women with HDP only from 1 Jan. 2019 to 31 Dec. 2021 within 40 participating neonatal intensive care units (NICUs) in Sino-northern network. ANS courses included completed, partial, repeated, and no ANS. Univariate and multivariable analyses were performed on administration of ANS and short-term outcomes before discharge. RESULTS: Among 1917 VPIs born to women with HDP only, 987(51.4%) received a complete course of ANS within 48 h to 7 days before birth, 560(29.2%) received partial ANS within 24 h before delivery, 100(5.2%) received repeat ANS and 270 (14.1%) did not receive any ANS. Compared to infants who received complete ANS, infants unexposed to ANS was associated with higher odds of death (AOR 1.85; 95%CI 1.10, 3.14), Severe Neurological Injury (SNI) or death (AOR 1.68; 95%CI 1.29,3.80) and NEC or death (AOR 1.78; 95%CI 1.55, 2.89), the repeated ANS group exhibits a significant negative correlation with the duration of oxygen therapy days (correlation coefficient - 18.3; 95%CI-39.2, -2.1). However, there were no significant differences observed between the full course and partial course groups in terms of outcomes. We can draw similar conclusions in the non-SGA group, while the differences are not significant in the SGA group. From KM curve, it showed that the repeated group had the highest survival rate, but the statistical analysis did not indicate a significant difference. CONCLUSIONS: Even partial courses of ANS administered within 24 h before delivery proved to be protective against death and other morbidities. The differences mentioned above are more pronounced in the non-SGA group. Repeat courses demonstrate a trend toward protection, but this still needs to be confirmed by larger samples.

Rich oxygen vacancies in confined heterostructured TiO2@In2S3 hybrid for boosting solar-driven CO2 reduction.

Solar energy driving CO2 reduction is a potential strategy that not only mitigates the greenhouse effect caused by high CO2 level in atmosphere, but also yields carbon chemicals/fuels at the same time. Herein, a facile way to design the heterogeneous TiO2@In2S3 hollow structures possessing robust light harvesting in both ultraviolet and visible regions is proposed and exhibits a higher generation rate of 25.35 and 1.24 µmol·g-1·h-1 for photocatalytic CO2 reduction to CO and CH4, respectively. The excellent photocatalytic catalytic performance comes from i) the confined heterostructured TiO2@In2S3 possesses a suitable band structure and a broadband-light absorbing capacity for CO2 photoreduction, ii) the rich interfaces between nanosized TiO2 and In2S3 on the shell can significantly reduce the diffusion length of carriers and enhance the utilization efficiency of photogenerated electron-hole pairs, and iii) enriched surface oxygen vacancies can provide more active sites for CO2 adsorption.

Association of Long Non-coding RNA C1RL-AS1 and PTPN6 Gene Polymorphisms with Ocular Behcet's Disease in Han Chinese.

PURPOSE: To explore the association of the polymorphisms in PTPN6 and LncRNA C1RL-AS1 genes with ocular BD in Han Chinese patients. METHODS: Correlation study was performed using the iPLEX system on a cohort of ocular BD patients andcontrols. The genotyping of 7 SNPs for LncRNA C1RL-AS1 and PTPN6 genes in ocular BD patients was performed using the iPLEX Gold genotype. RESULTS: The frequencies of rs4013722 AG genotype/A allele in LncRNA C1RL-AS1 were significantly decreased in BD patients, and the frequency of GG genotype was significantly increased in BD patients. The rs4013722 was associated with ocular BD in male patients, but not in female patients. The AG and GG genotype of rs4013722 were associated with skin lesions in male patients. The gene polymorphisms of PTPN6 were not associated with BD patients. CONCLUSIONS: The LncRNA C1RL-AS1/rs4013722 polymorphism conferred susceptibility to ocular BD in Han Chinese patients, which was influenced by sex.Abbreviations: LncRNA: Long Non-coding RNA; BD: Behcet's disease; SNP: single nucleotide polymorphism; PBMCs: peripheral blood mononuclear cells; PTPs: Protein tyrosine phosphatases; PTPN6: protein tyrosine phosphatase non-receptor 6; GWAS: genome-wide association study; HWE: Hardy-Weinberg equilibrium; LD: linkage disequilibrium; OR: odds ratio; CI: confidence interval; eQTL: expression quantitative trait loci; IBD: inflammatory bowel disease; RA: rheumatoid arthritis; Padj: Bonferroni corrected P value; NS: non-significant.

Substation of vermicompost mitigates Cd toxicity, improves rice yields and restores bacterial community in a Cd-contaminated soil in Southern China.

Cadmium (Cd) contamination in agricultural soil is a global concern for soil health and food sustainability because it can cause Cd accumulation in cereal grains. An in-situ stabilizing technology (using organic amendments) has been widely used for Cd remediation in arable lands. Therefore, the current study examined the influence of vermicompost (VC) on soil biochemical traits, bacterial community diversity and composition, Cd uptake and accumulation in rice plants and grain yield in a Cd-contaminated soil during the late growing season in 2022. Different doses of VC (i.e., V1 = 0 t ha-1, V2 = 3 t ha-1 and V3 = 6 t ha-1) and two concentrations of Cd (i.e., Cd1 = 0 and Cd2 = 50 mg Cd Kg-1 were used. We performed high-throughput sequencing of 16S ribosomal RNA gene amplicons to characterize soil bacterial communities. The addition of VC considerably affected the diversity and composition of the soil bacterial community; and increased the relative abundance of phyla Chloroflexi, Proteobacteria, Acidobacteriota, Plantomycetota, Gemmatimonadota, Patescibacteria and Firmicute. In addition, VC application, particularly High VC treatment, exhibited the highest bacterial diversity and richness (i.e., Simpson, Shannon, ACE, and Chao 1 indexes) of all treatments. Similarly, the VC application increased the soil chemical traits, including soil pH, soil organic carbon (SOC), available nitrogen (AN), total nitrogen (TN), total potassium (TK), total phosphorous (TP) and enzyme activities (i.e., acid phosphatase, catalase, urease and invertase) compared to non-VC treated soil under Cd stress. The average increase in SOC, TN, AN, TK and TP were 5.75%, 41.15%, 18.51%, 12.31%, 25.45% and 29.67%, respectively, in the High VC treatment (Pos-Cd + VC3) compared with Cd stressed soil. Redundancy analysis revealed that the leading bacterial phyla were associated with SOC, AN, TN, TP and pH, although the relative abundance of Firmicutes, Proteobacteria, Bacteroidata, and Acidobacteria on a phylum basis and Actinobacteria, Gammaproteobacteria and Myxococcia on a class basis, were highly correlated with soil environmental factors. Moreover, the VC application counteracted the adverse effects of Cd on plants and significantly reduced the Cd uptake and accumulation in rice organs, such as roots, stem + leaves and grain under Cd stress conditions. Similarly, applying VC significantly increased the fragrant rice grain yield and yield traits under Cd toxicity. The correlation analysis showed that the increased soil quantities traits were crucial in obtaining high rice grain yield. Generally, the findings of this research demonstrate that the application of VC in paddy fields could be useful for growers in Southern China by sustainably enhancing soil functionality and crop production.

Phosphorus fertiliser application mitigates the negative effects of microplastic on soil microbes and rice growth.

Soil microplastics (MPs) have attracted widespread attention recently. Most studies have explored how soil MPs affect the soil's physicochemical parameters, matter circulation, and soil microbial community assembly. Similarly, a key concern in agricultural development has been the use of phosphorus (P) fertiliser, which is essential for plant health and development. However, the relationship between MPs and phosphate fertilisers and their effects on the soil environment and plant growth remains elusive. This study assessed the influence of adding low-density polyethylene MPs (1%) with different phosphate fertiliser application rates on microbial communities and rice biomass. Our results showed that MPs changed the structure of soil bacterial and phoD-harbouring microbial communities in the treatment with P fertiliser at the same level and suppressed the interactions of phoD-harbouring microorganisms. In addition, we found that MPs contamination inhibited rice growth; however, the inclusion of P fertiliser in MP-contaminated soils reduced the inhibitory action of MPs on rice growth, probably because the presence with P fertiliser promoted the uptake of NO3--N by rice in MP-contaminated soils. Our results provide further insights into guiding agricultural production, improving agricultural management, and rationally applying phosphate fertilisers in the context of widespread MPs pollution and global P resource constraints.

Resection of bilateral massive Achilles tendon xanthomata with reconstruction using vascularized iliotibial tract: A case report and literature review.

RATIONALE: Cerebrotendinous xanthomatosis is a rare autosomal recessive metabolic disease. Surgical treatment is only indicated when the xanthoma becomes large, painful, and irritable with shoe wear. Reconstruction of the large defect following resection challenging, especially with resection of the entire Achilles tendon. PATIENT CONCERNS: We report a case of bilateral Achilles tendon defects of 16 cm following resection of bilateral Achilles tendon xanthomata, with reconstruction using vascularized iliotibial tract. The patient had a good functional outcome with well-preserved strength and cosmesis. OUTCOMES: Reconstruction of a total Achilles tendon defect using Vascularized iliotibial tract is safe and effective.

BR109, a Novel Fully Humanized T-Cell-Engaging Bispecific Antibody with GPRC5D Binding, Has Potent Antitumor Activities in Multiple Myeloma.

At present, multiple myeloma (MM) is still an essentially incurable hematologic malignancy. Although BCMA-targeted therapies have achieved remarkable results, BCMA levels were found to be downregulated in patients with MM who relapsed after these treatments. Therefore, the search for other antigens specific to MM has become a priority. Independently of BCMA expression, G-protein-coupled receptor family C group 5 member D (GPRC5D) is mainly expressed in the plasma cells of MM patients, while it is expressed in a limited number of normal tissues. Combining MM-specific antigen GPRC5D and T-cell-mediated therapies would be a promising therapeutic strategy for MM. Recently, we constructed a new anti-GPRC5D × anti-CD3 T-cell-engaging bispecific antibody (TCB), BR109, which was capable of binding to human GPRC5D and human CD3ε. Moreover, BR109 was proven to have relatively good stability and antitumor activity. BR109 could specifically trigger T-cell-mediated cytotoxicity against many GPRC5D-positive MM cells in vitro. Meanwhile, antitumor activity was demonstrated in MM cell line xenograft mouse models with human immune cell reconstitution. These preclinical studies have formed a solid foundation for the evaluation of MM treatment efficacy in clinical trials.

Effect of different types of biochar on soil properties and functional microbial communities in rhizosphere and bulk soils and their relationship with CH4 and N2O emissions.

Biochar as an agricultural soil amendment plays vital roles in mediating methane (CH4) and nitrous oxide (N2O) emissions in soils. The link between different types of biochar, bulk soil, and rhizosphere microbial communities in relation to CH4 and N2O emissions is being investigated in this study. The rice pot experiment was conducted using biochar at two temperatures (300°C and 500°C) in combination with three biochar levels (0, 2, 10% w/w). Soil properties and the abundance of genes associated with CH4 and N2O emissions from both rhizosphere and bulk soils were investigated. The study also aimed to examine the structure of microbial communities (pmoA, nosZ) in rhizosphere and bulk soils whereas CH4 and N2O emissions were monitored while growing rice. Results showed that biochar at 300°C and 10% incorporation significantly increased the CH4 emissions by up to 59% rise compared to the control group. Random Forest analysis revealed that the ratio of mcrA/pmoA along with the abundance of mcrA from both rhizosphere and bulk soils, the abundance of AOA, TN, DOC, and the community composition of pmoA-harboring microorganisms from both bulk and rhizosphere soils were important predictors of CH4 emissions. Therefore, the ratio of mcrA/pmoA in rhizosphere soil and the abundance of AOA in bulk soil were the main factors influencing CH4 emissions. Variation Partitioning Analysis (VPA) results indicated that the effects of these factors on bulk soil were 9% of CH4 emissions variations in different treatments, which contributed more than rhizosphere soils' factors. Moreover, random forest analysis results indicated that the abundance of AOB in bulk soil was the most important predictor influencing N2O emissions. The VPA result revealed that the factors in rhizosphere soil could explain more than 28% of the variations in N2O emissions. Our study highlights that rhizosphere soil has a more significant effect than bulk soil on N2O production. Our findings further the understanding of the link between bulk and rhizosphere attributes, and their impact on CH4 and N2O emissions in paddy soils. In summary, we recommend the application of biochar at 500°C and 2% incorporation rate for agricultural production in the area.

Design, Synthesis, Structure-Activity Relationship, and Three-Dimensional Quantitative Structure-Activity Relationship of Fusarium Acid Derivatives and Analogues as Potential Fungicides.

In research related to fungicides, the development of compounds from natural products with high antifungal activity has attracted considerable attention. Fusaric acid (FA), an alkaloid isolated from the metabolites of Fusarium oxysporum, is an important precursor for developing pharmacologically active herbicides. In our previous work, we reported that FA has a wide range of inhibitory activities against 14 plant pathogenic fungi. In particular, it exhibited excellent antifugal effects on Colletotrichum higginsianum (EC50 = 31.7 µg/mL). Herein, to explore the practical application in the agricultural field, the design and synthesis of three series of FA derivatives and their inhibitory activities against plant pathogenic fungi were examined. Results demonstrated that the optimized FA derivatives had excellent inhibitory activities against C. higginsianum, Helminthosporium (Harpophora maydis), and Pyricularia grisea. In particular, the inhibitory activities were considerably improved when the 5-butyl groups of FA were substituted. The EC50 of C. higginsianum and P. grisea was only 1.2 and 12.0 µg/mL when 5-butylalkyl groups were substituted with 5-([1,1'-biphenyl]-4-yl) and 5-phenyl, respectively. Moreover, the safety index of target compounds, which was obtained from the treatment index of medicines, on rice seeds was evaluated. Finally, 16 leading compounds (H4, H22-H24, H27, H29, H30-H34, H37, H45, H50, H52, and H53) were obtained; they had considerable potential for additional modification and optimization as agricultural fungicides. Moreover, three-dimensional quantitative structure-activity relationship models were developed for obtaining a systematic structure-activity relationship profile to explore the possibility of more potent FA derivatives as novel fungicides.

A Fluid-Driven Loop-Type Modular Soft Robot with Integrated Locomotion and Manipulation Capability.

In nature, some animals, such as snakes and octopuses, use their limited body structure to conduct various complicated tasks not only for locomotion but also for hunting. Their body segments seem to possess the intelligence to adapt to environments and tasks. Inspired by nature, a modular soft robot with integrated locomotion and manipulation abilities is presented in this paper. A soft modular robot is assembled using several homogeneous cubic pneumatic soft actuator units made of silicone rubber. Both a mathematical model and backpropagation neural network are established to describe the nonlinear deformation of the soft actuator unit. The locomotion process of the chain-type soft robot is analyzed to provide a general rhythmic control principle for modular soft robots. A vision sensor is adopted to control the locomotion and manipulation processes of the modular soft robot in a closed loop. The experimental results indicate that the modular soft robot put forward in this paper has both locomotion and manipulation abilities.

In Situ Fabrication of SnS2/SnO2 Heterostructures for Boosting Formaldehyde-Sensing Properties at Room Temperature.

Formaldehyde, as a harmful gas produced by materials used for decorative purposes, has a serious impact on human health, and is also the focus and difficulty of indoor environmental polution prevention; hence, designing and developing gas sensors for the selective measurement of formaldehyde at room temperature is an urgent task. Herein, a series of SnS2/SnO2 composites with hollow spherical structures were prepared by a facile hydrothermal approach for the purpose of formaldehyde sensing at room temperature. These novel hierarchical structured SnS2/SnO2 composites-based gas sensors demonstrate remarkable selectivity towards formaldehyde within the concentration range of sub-ppm (0.1 ppm) to ppm (10 ppm) at room temperature. Notably, the SnS2/SnO2-2 sensor exhibits an exceptional formaldehyde-sensing performance, featuring an ultra-high response (1.93, 0.1 ppm and 17.51, 10 ppm), as well as good repeatability, long-term stability, and an outstanding theoretical detection limit. The superior sensing capabilities of the SnS2/SnO2 composites can be attributed to multiple factors, including enhanced formaldehyde adsorption, larger specific surface area and porosity of the hollow structure, as well as the synergistic interfacial incorporation of the SnS2/SnO2 heterojunction. Overall, the excellent gas sensing performance of SnS2/SnO2 hollow spheres has opened up a new way for their detection of trace formaldehyde at room temperature.

Research on application of radiomics in glioma: a bibliometric and visual analysis.

Background: With the continuous development of medical imaging informatics technology, radiomics has become a new and evolving field in medical applications. Radiomics aims to be an aid to support clinical decision making by extracting quantitative features from medical images and has a very wide range of applications. The purpose of this study was to perform a bibliometric and visual analysis of scientific results and research trends in the research application of radiomics in glioma. Methods: We searched the Web of Science Core Collection (WOScc) for publications related to glioma radiomics. A bibliometric and visual analysis of online publications in this field related to countries/regions, authors, journals, references and keywords was performed using CiteSpace and R software. Results: A total of 587 relevant literature published from 2012 to September 2022 were retrieved in WOScc, and finally a total of 484 publications were obtained according to the filtering criteria, including 393 (81.20%) articles and 91 (18.80%) reviews. The number of relevant publications increases year by year. The highest number of publications was from the USA (171 articles, 35.33%) and China (170 articles, 35.12%). The research institution with the highest number of publications was Chinese Acad Sci (24), followed by Univ Penn (22) and Fudan Univ (21). WANG Y (27) had the most publications, followed by LI Y (22), and WANG J (20). Among the 555 co-cited authors, LOUIS DN (207) and KICKINGEREDER P (207) were the most cited authors. FRONTIERS IN ONCOLOGY (42) was the most published journal and NEURO-ONCOLOGY (412) was the most co-cited journal. The most frequent keywords in all publications included glioblastoma (187), survival (136), classification (131), magnetic resonance imaging (113), machine learning (100), tumor (82), and feature (79), central nervous system (66), IDH (57), and radiomics (55). Cluster analysis was performed on the basis of keyword co-occurrence, and a total of 16 clusters were formed, indicating that these directions are the current hotspots of radiomics research applications in glioma and may be the future directions of continuous development. Conclusion: In the past decade, radiomics has received much attention in the medical field and has been widely used in clinical research applications. Cooperation and communication between countries/regions need to be enhanced in future research to promote the development of radiomics in the field of medicine. In addition, the application of radiomics has improved the accuracy of pre-treatment diagnosis, efficacy prediction and prognosis assessment of glioma and helped to promote the development into precision medicine, the future still faces many challenges.

Effectiveness and safety of REBACIN as a non-invasive intervention for persistent high-risk human papillomavirus infection: A real-world prospective multicenter cohort study.

BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.

Micro-simulation insights into the functional and mechanistic understanding of glycyrrhizin against asthma.

Asthma is a common chronic respiratory disease, which causes inflammation and airway stenosis, leading to dyspnea, wheezing and chest tightness. Using transgelin-2 as a target, we virtually screened the lead compound glycyrrhizin from the self-built database of anti-asthma compounds by molecular docking technology, and found that it had anti-inflammatory, anti-oxidative and anti-asthma pharmacological effects. Then, molecular dynamics simulations were used to confirm the stability of the glycyrrhizin-transgelin-2 complex from a dynamic perspective, and the hydrophilic domains of glycyrrhizin was found to have the effect of targeting transgelin-2. Due to the self-assembly properties of glycyrrhizin, we explored the formation process and mechanism of the self-assembly system using self-assembly simulations, and found that hydrogen bonding and hydrophobic interactions were the main driving forces. Because of the synergistic effect of glycyrrhizin and salbutamol in improving asthma, we revealed the mechanism through simulation, and believed that salbutamol adhered to the surface of the glycyrrhizin nano-drug delivery system through hydrogen bonding and hydrophobic interactions, using the targeting effect of the hydrophilic domains of glycyrrhizin to reach the pathological parts and play a synergistic anti-asthmatic role. Finally, we used network pharmacology to predict the molecular mechanisms of glycyrrhizin against asthma, which indicated the direction for its clinical transformation.